Luteolin Activates ERK1/2- and Ca-dependent HO-1 Induction That Reduces LPS-induced HMGB1, INOS/NO, and COX-2 Expression in RAW264.7 Cells and Mitigates Acute Lung Injury of Endotoxin Mice

Overview

Journal Inflamm Res

Specialties Allergy & Immunology
Pathology

Date 2018 Mar 3

PMID 29497773

Citations 26

Authors

Eun Jung Park

Young Min Kim

Hye Jung Kim

Ki Churl Chang

Affiliations

Soon will be listed here.

Abstract

Objective: Although luteolin has shown to have anti-inflammatory action, no report is available whether luteolin inhibits HMGB1 and protects acute lung injury (ALI) in endotoxin rodents. We hypothesized that HO-1 induction by luteolin might play a crucial role for inhibition of pro-inflammatory mediators including HMGB1 through MAPK signaling in LPS-induced RAW264.7 cells, and it ameliorates ALI of endotoxin mice.

Methods: The effects of luteolin on the production of pro-inflammatory mediators in LPS-activated RAW264.7 cells and LPS-injected mice were evaluated. The mechanisms were investigated using various signal inhibitors.

Results: Luteolin significantly increased HO-1 expression through ERK1/2 signaling in a time- and concentration-dependent manner. Indeed, luteolin inhibited pro-inflammatory mediators (HMGB1, iNOS/NO, COX-2, and NF-κB activity) in LPS-activated RAW264.7 cells. In addition, PD98059, an ERK1/2 inhibitor, treatment failed to inhibit production of these pro-inflammatory mediators by luteolin. Interestingly, luteolin augmented HO-1 induction through Ca influx in RAW264.7 cells. Administration of luteolin significantly inhibited plasma HMGB1 level, and iNOS expression in the lung that resulted in a significant reduction of ALI in endotoxin mice that was reversed by a HO-1 inhibitor, ZnPPIX.

Conclusion: Therefore, we conclude that luteolin has a great potential for treatment of ALI and related diseases, where HMGB1 is a therapeutic target.

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